X-Meeting presentations

IN SILICO ANALYSIS OF THE PHARMACODYNAMIC PROFILE OF A THIAZOLE DERIVATIVE AGAINST BACTERIAL TARGETS

Published in 21/11/2024 - ISBN: 978-65-272-0843-3

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Paper Title
IN SILICO ANALYSIS OF THE PHARMACODYNAMIC PROFILE OF A THIAZOLE DERIVATIVE AGAINST BACTERIAL TARGETS
Authors
  • Caio Victor Silva Soares
  • Antonio Miguelsinho Martins de Sousa FIlho
  • João Pedro Pereira Gomes
  • Jamerson Ferreira de Oliveira
Modality
Poster
Subject area
Systems Biology and Modeling
Publishing Date
21/11/2024
Country of Publishing
Brazil | Brasil
Language of Publishing
Inglês
Paper Page
https://www.even3.com.br/anais/xmeeting-2024/833027-in-silico-analysis-of-the-pharmacodynamic-profile-of-a-thiazole-derivative-against-bacterial-targets
ISBN
978-65-272-0843-3
Keywords
Molecular Docking, Thiazole and Antibacterial
Summary
Heterocycles are considered privileged frameworks within medicinal chemistry, becoming planning targets for obtaining new compounds with biological activity. The thiazole, belonging to the family of azole heterocycles, is seen as an alternative in the development of molecules with little explored mechanisms of action, presenting itself as a possible solution for microorganisms resistant to current therapy. Related to bactericidal action, one can investigate the interaction of Thiazole derivatives with DNA gyrase, an important enzyme for the process of duplication of genetic material, as it is responsible for catalyzing the breakage of the two DNA strands, and glutathione S-transferase (GST) involved in the microorganism detoxification process, by promoting the conjugation of xenobiotics with glutathione. This study aims to analyze the antimicrobial potential of a thiazole derivative TZ-03 synthesized by the Organic Chemistry Laboratory Applied to Drugs (LAQOFAR-UNILAB) drawn from in silico pharmacodynamic predictions, using the molecular docking technique. Initially, the targets DNA gyrase (PDB ID: 6KZV) and GST (PDB ID: 1A0F) were removed from the Protein Data Bank. Regarding the design and minimization of the compounds energy, the software Marvinsketch and ArgusLab were used. Afterwards, to carry out molecular docking, GOLD 2024.1.0 (Genetic Optimization for Ligand Docking) was used, considering the score functions with the lowest RMSD value obtained with redocking. Visualization of target-ligand interactions occurred through the Discovery Studio 2024 Client. Thus, it was observed that, among the macromolecular complexes obtained, TZ-03 showed a significant conjugation capacity with the DNA-gyrase target (58.19 vs 62.47), but not enough to overcome the co-crystallized ligand. Regarding GST, the fitscore results demonstrated a low affinity for the target enzyme (50.53 vs 66.43), suggesting a lesser interaction with glutathione S-transferase in vivo. When individually analyzing the interactions with GST, it is clear that the amino acids Cys-10 and His-106 are important for the formation of pi-alkyl and pi-sulfur interactions, respectively, with the phenyl and thiazole groups of TZ-03. However, the formation of an unfavorable interaction in the proximity of hydrogen bond acceptor groups destabilizes the target-ligand complex. Regarding DNA gyrase, the presence of relevant electrostatic pi-cation and pi-anion interactions with the protein residues Glu-50 and Arg-76 is observed, as well as the formation of a hydrogen bond with the amino acid Gly-77. Furthermore, the presence of chlorine in one of the aromatic rings was decisive for the formation of important hydrophobic interactions with the target. Finally, a possible affinity of TZ-03 towards DNA-gyrase can be seen, requiring new in vitro pharmacodynamic studies to confirm its biological activity.
Title of the Event
20º Congresso Brasileiro de Bioinformática: X-Meeting 2024
City of the Event
Salvador
Title of the Proceedings of the event
X-Meeting presentations
Name of the Publisher
Even3
Means of Dissemination
Meio Digital

How to cite

SOARES, Caio Victor Silva et al.. IN SILICO ANALYSIS OF THE PHARMACODYNAMIC PROFILE OF A THIAZOLE DERIVATIVE AGAINST BACTERIAL TARGETS.. In: X-Meeting presentations. Anais...Salvador(BA) Hotel Deville Prime, 2024. Available in: https//www.even3.com.br/anais/xmeeting-2024/833027-IN-SILICO-ANALYSIS-OF-THE-PHARMACODYNAMIC-PROFILE-OF-A-THIAZOLE-DERIVATIVE-AGAINST-BACTERIAL-TARGETS. Access in: 15/10/2025

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